Mutations in LCA5 are an uncommon cause of Leber congenital amaurosis (LCA) type II

Abstract

Leber congenital amaurosis (LCA) is the earliest and most severe form of inherited retinal dystrophy responsible for blindness or severe visual impairment at birth or within the first months of life. Up to date, ten LCA genes have been identified. Three of them account for ca. 43% of families and are responsible for a congenital severe stationary cone-rod dystrophy (Type I, 60 % of LCA) while the seven remaining genes account for 32% of patients and are responsible for a progressive yet severe rod-cone dystrophy (Type II, 40 % of LCA ). Recently, mutations in LCA5, encoding the ciliary protein lebercilin, were reported to be a rare cause of leber congenital amaurosis. The purpose of this study was to evaluate the involvement of this novel gene and to look for genotype-phenotype correlations. Here we report the identification of three novel LCA5 mutations (3/3 homozygous) in three families confirming the modest implication of this gene in our series (3/179; 1.7%). Besides, we suggest that the phenotype of these patients affected with a particularly severe form of LCA type II may represent a continuum with LCA type I.

Screening of a Large Cohort of Leber Congenital Amaurosis and Retinitis Pigmentosa Patients Identifies Novel LCA5 Mutations and New Genotype-Phenotype Correlations

“…Previously, and in the majority of patients in this study, the phenotype reported in association with LCA5 mutations is consistent with LCA with severely reduced vision at, or near birth, nystagmus, and a nondetectable (<10 μV) ERG [Ahmad et al, 2011;den Hollander et al, 2007;Dharmaraj et al, 2000;Gerber et al, 2007;Jacobson et al, 2009;Mohamed et al, 2003;Ramprasad et al, 2008]. High hypermetropia is common.…”

“…To date, 12 different mutations in LCA5 have been reported. In patients of all families except one, the phenotype has been typical of LCA [Abu-Safieh et al, 2013;Ahmad et al, 2011;den Hollander et al, 2007;Gerber et al, 2007;Jacobson et al, 2009;Li et al, 2011;Ramprasad et al, 2008;Vallespin et al, 2010a;Vallespin et al, 2010b]. Despite its ubiquitous expression and its crucial functions in the cilia [Boldt et al, 2011], the phenotype associated with LCA5 mutations has thus far been confined to the retina.…”

Identification of Mutations Causing Inherited Retinal Degenerations in the Israeli and Palestinian Populations Using Homozygosity Mapping

“…4,42 Mutations in LCA5 cause early-onset and severe visual disturbance with nystagmus, abnormal VA, extinguished ERGs, and fundus features of severe retinal degeneration. 4, 43 We identified a consanguineous Arab-Muslim family (MOL0615) with one affected child who was diagnosed with LCA (Fig. 3).…”

Abnormal respiratory cilia in non-syndromic Leber congenital amaurosis with CEP290 mutations

“…Conversely to RPGRIP1 and TULP1 which are specifically or preferentially expressed in the retina,5 6 LCA5 and CEP290 are expressed in various ciliated tissues 7 8. To our knowledge, LCA5 mutations were reported in few patients only affected with non-syndromic LCA 8 9. Yet, CEP290 mutations were shown to be a frequent cause of non-syndromic LCA as well as syndromic LCA including Joubert syndrome, ( JBTS5 , MIM610188) Senior–Loken syndrome, ( SLSN6 , MIM610189) Meckel syndrome ( MKS4 , MIM611134) and possibly Bardet–Bield syndrome (BBS14, MIM610142).…”